rs11247593

chr1-26725589-G-Achr1-26725589-G-Cchr1-26725589-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006015.6(ARID1A):c.1138-4062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,956 control chromosomes in the GnomAD database, including 9,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9487 hom., cov: 31)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

ARID1A (HGNC:11110): (AT-rich interaction domain 1A) This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1A	NM_006015.6	c.1138-4062G>A		intron_variant		ENST00000324856.13
ARID1A	NM_139135.4	c.1138-4062G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1A	ENST00000324856.13	c.1138-4062G>A		intron_variant		1	NM_006015.6
ARID1A	ENST00000430799.7	c.-12-4062G>A		intron_variant		5		A2
ARID1A	ENST00000457599.6	c.1138-4062G>A		intron_variant		5
ARID1A	ENST00000637465.1	c.-12-4062G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47317 AN: 151838 Hom.: 9475 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47353 AN: 151956 Hom.: 9487 Cov.: 31 AF XY: 0.321 AC XY: 23868 AN XY: 74282

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.349

Alfa AF: 0.247 Hom.: 9590

Bravo AF: 0.338

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	10
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11247593; hg19: chr1-27052080;